tbuckley/cabot-search huggingface dataset:
Abstract 15813: Comparative Case Series of Biventricular Support Between Heartmate-3 Ventricular Assist Devices and the Total Artificial Heart: A Single-Center Experience
Authors: Mohan Satish, Julie Roldan, Noah Moss, Ani Anyanwu, Donna M Mancini
Journal: Circulation (2022)

Introduction: Currently, only the Syncardia Total Artificial Heart (TAH) is approved for biventricular support as a bridge-to-transplant (BTT). The off-label use of continuous flow ventricular assist devices (VAD) in a biventricular configuration (BiVAD) has been used with variable results, emphasizing the need for patient selection. We report our single-center BiVAD experience in patients supported with two HeartMate-3 (HM-3) VADs in a biventricular configuration in comparison with TAH support. Methods: All patients receiving durable biventricular mechanical support at The Mount Sinai Hospital (New York, New York) were considered. Baseline clinical, echocardiographic, hemodynamic and outcome data were extracted. Outcomes of interest were postoperative survival and adverse events, and compared using non-parametric statistics. Successful BTT and post-transplant survival were descriptively evaluated. Results: From November 2018 through May 2022, a total of 6 (37.5%) patients received two HM-3 VAD pumps in a BiVAD configuration and 10 (62.5%) patients received a TAH. Overall, TAH patients had significantly higher median INTERMACS profiles (p &lt; 0.05) at baseline compared to those on HM-3 BiVAD support but lower 30-day and 6-month survival and with a significantly higher rate of renal failure (Table 1). However, survival declined to the same rate at 1-year with both forms of support and was largely due to extracardiac adverse events related to underlying comorbidities (particularly, CKD/ESRD and diabetes, p &lt; 0.05). Successful BTT has thus far been achieved in 2 (33%) HM-3 BiVAD compared to 5 (50%) TAH patients, and had similar post-transplant survival at 1-year. Conclusions: HM-3 BiVAD demonstrated lower short-term and similar long-term mortality compared to TAH support among patients in extremis. However, larger studies are needed to optimize patient selection and pursuit of mechanical support in biventricular failure.
Abstract 15875: Poorer Arterial Compliance is Associated With Decreased Cognitive Function: The Bogalusa Heart Study
Authors: Ileana De Anda-Duran, Antonio Duran, Camilo F Alonso, David Libon, Lydia Bazzano
Journal: Circulation (2022)

Introduction: Pathological arterial stiffness has been linked to lower cognitive function (CF) in the elderly. However, information is scarce on the association between poorer arterial compliance and decreased cognitive function among middle-aged adults and whether sex and/or race modify this association. We explored this observation among noninstitutionalized individuals living in a rural community. Methods: This cross-sectional analysis considered 1,228 adult participants of the Bogalusa Heart Study (mean age 48.2 ± 5.3 years, 57.6% female, 33.1% Black) that completed standardized neuropsychological (NP) assessments to evaluate CF and non-invasive pulse-wave velocity (PWV) measurements to explore arterial compliance. CF was expressed as a global cognitive score (GCS). GCS and PVW were divided into quartiles, and multivariable-adjusted binary logistic regression models were employed to determine the association between the upper quartile (Q4) of PVW (poorer compliance) and the lower quartile (Q1) of GCS (decreased cognitive function), controlling for traditional CMRF, education and depression status. Race, sex, and PWV interactions were tested to explore effect modification. Results: In contrast to their counterparts, Blacks and males had lower GCS (p&lt;0.001); whereas PVW was higher among Blacks and males (p&lt;0.01). Following a significant sex*PVW interaction term, sex-specific models yielded a significant independent association between Q4 PVW and Q1 GCS (OR: 1.9, 95%CI: 1.2-3.1, p&lt;0.01) in males only. Race did not modify this association. Conclusion: Poorer arterial compliance is associated with decreased cognitive function during midlife in males but not females. These findings underscore the need to introduce patient-centered, early management strategies to control arterial compliance, potentially considering a sex-specific approach, even in the absence of overt hypertension, to lower the risk of cognitive impairment typically associated with aging.
Abstract 15659: Development of Novel EMAP-II Neutralizing Antibody Therapy for HIV-Associated Pulmonary Hypertension via Abrogation of HIV-Nef Induced Pulmonary Endothelial Damage
Authors: Sarvesh Chelvanambi, Moraima Noda, Matthias A Clauss
Journal: Circulation (2022)

Rationale: People living with HIV experience increased rates of cardiovascular co-morbidities including pulmonary hypertension (600-fold higher prevalence) despite immediate prescription of combined antiviral therapy (ART) upon HIV diagnosis. Previously, we reported that the virally encoded HIV-Nef protein persists in extracellular vesicles (EV) isolated from bronchoalveolar lavage fluid of aviremic HIV patients on ART. Interestingly, Nef-positivity correlated with increased EMAPII levels, a cellular protein which when released extracellularly specifically amplifies endothelial apoptosis. We hypothesize that Nef-EMAPII signaling axis induces endothelial apoptosis and senescence, which could give rise to apoptosis-senescence-resistant, plexiform lesion-forming endothelial cells. Methods and Results: Co-culture with Nef EV producing SupT1 T-cells induces endothelial senescence quantified using senescence associated marker-p16INK4a (p&lt;0.001) which corresponds to increased EMAPII surface expression. Nef induced endothelial senescence as quantified by β-Galactosidase activity was blocked with EMAPII neutralizing antibody (Fig). Transgenic mice with endothelium specific Nef expression had elevated EMAP II surface expression. Two-dose injection of EMAPII neutralizing antibodies (1 mg/mouse, sc) abrogates apoptosis induction as determined by cleaved caspase 3+ pulmonary endothelial cells (p&lt;0.001). Furthermore, Nef Tg mice derived pulmonary endothelial cells had reduced colony formation (p&lt;0.001) which is being tested with EMAPII neutralization as a therapeutic agent. Conclusion: Nef induced apoptosis and cellular senescence can be targeted with EMAP II neutralizing antibodies both in vitro and in vivo . These data suggest that A) Nef can give rise to apoptosis-senescence-resistant plexiform lesion forming endothelial cells and B) neutralizing EMAPII antibodies can be employed to block progression of PAH.
Abstract 15819: Longing for a Pacemaker, Association of Prolonged Qrs and Permanent Pacemaker in the Tavr Population
Authors: Carlos A Dohse, Pranati Sreepathy, Zaid Zayyad, David Polman, Siddharth Bhayani, Aamir Twing, Manoj Ambalavanan, Rachel Brett, Farrah Nasrollahi, Keshav Patel, David Tiu, Helena Dickens, Mayank M Kansal, Khalil Ibrahim, Adhir R Shroff
Journal: Circulation (2022)

Background: The duration of the QRS carries valuable information regarding structural disease, conduction defects, or even ischemia. Studies have shown that a widened QRS (&gt;120) is associated with poor cardiovascular outcomes. In this study we investigated the impact of the presence of a widened QRS (wQRS )previous to Transcatheter Aortic Valve Replacement (TAVR) and clinical outcomes. Methods:: Retrospective analysis of electronic medical records from 2018-2020 at the University of Illinois Chicago identified TAVR patients. Patients were placed into two groups: a wQRS and a nQRS group. Those with pacemakers prior to procedure were excluded. Primary outcomes included PPM placement prior to discharge, composite MACE (all-cause mortality, MI, or CVA), and (LOS) at 6 and 12 months. Results: We included 149 patients in this analysis. There were 76.1% male, 57.1% non-white, and 74 ± 13 years old on average. A wQRS was found in 46 (30.9%) and 103 (69.1%) were found to have a nQRS. Of this group, 40.2% had a history of congestive heart failure (CHF). The average ejection fraction (EF) was 50% with 80% of patients having a normal (EF). The CoreValve was placed in 65.7% of patient compared to 34.3% of patients having the Sapian valve placed. There were no differences in age, sex, or race between the two groups. Of all patient’s in the study, those with a wQRS were more likely to have a PPM placed prior to discharge compared to those with nQRS (17.4% (8) vs 5.8% (6) , p=0.025). Though not significant, 14% (13)of patients with the CoreValve placed required PPM prior to discharge compared to 2.5%(1) in the Sapian valve group (p=.175). There was no statistically significant difference in composite MACE, LOS, or significant bleeding events in either groups at 6 or 12 months. Conclusion: Our results suggest that patients with a wQRS are more likely to receive a PPM placement post TAVR during index hospitalization compared to those with a nQRS. This study suggests further investigation into the predictive nature of EKG parameters on clinical outcomes be done.
Abstract 15751: Trends and Disparities in Pulmonary Arterial Hypertension Over the Past Decade: A National Inpatient Sample Database Study
Authors: Muhammad Khawar Sana, IRIAGBONSE ASEMOTA, Dae Yong Park, Hasan Hammo, Mahir Yilmaz, Mukunthan Murthi, Bharosa Sharma, Hafeez Shaka
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) is well defined, however, the trends and disparities have not been studied recently after the update in guidelines. Methods: We utilized National Inpatient Sample Database 2010-2019 to identify the cohort with principal diagnosis of PAH using ICD-9 and 10 codes. Primary outcome analysis included the crude admission rate of PAH per 1,000,000 adult hospitalizations during each calendar year stratified by sex, race, and median household income (MHOI). Secondary outcome analysis included trends in inpatient mortality rate, mean length of hospital stay (LOS), and mean total hospital charges (THC). Results: There were a total of 341 million admissions from 2010-2019 out of which 0.004% (13644) were adults admitted with principal diagnosis of PAH. There was no significant difference in year on year admissions in the last decade (Figure). Most patients were aged 18-65 when diagnosed (OR 1.73, 95% CI 1.55-1.92). Females were twice as likely to be diagnosed with PAH than males (OR 2.40, 95% CI 2.17-2.64). African Americans (OR 1.35, 95% CI 1.21-1.50) and Asian/Pacific Islander (OR 1.22, 95% CI 1.04-1.42) were at slightly more risk of PAH. There was no significant difference in inpatient mortality among patients with principal diagnosis of PAH over the last decade. Although mortality increased with increasing age (OR 1.29. 95% CI 1.29-3.33 for age &gt; 65) (OR 1.79, 95% CI 1.45-2.77) but did not defer when stratified for gender , race or year. Conclusion: Admissions for principal diagnosis of pulmonary arterial hypertension have remained unchanged over the last decade. Female sex, age and median house hold income is associated with increased risk for PAH.
Abstract 15698: Logistic and Machine Learning Approaches to Identify Predictors of Venous Thromboembolism in Covid-19 Patients
Authors: Manuela F Sacioto, Warley C Silveira, Suely Rezende, Bruno B Paiva, Magda C Pires, Cláudio Valiense, Marcos A Gonçalves, Polianna D Pereira, Milena Marcolino
Journal: Circulation (2022)

Introduction: Venous thromboembolism (VTE) has a significantly higher incidence in COVID-19 patients when compared to other acute viral infections. The evidence on the risk factors of VTE in COVID-19 inhospital patients is still inconsistent. The information is of utmost importance, as a path to promote prevention, early diagnosis and treatment. Hypothesis: VTE predictors may be identified through logistic regression (LR) and machine learning (ML) approaches. Methods: This multicenter cohort study included consecutive COVID-19 adult patients from 16 hospitals, admitted between March and September, 2020. Deep venous thrombosis and pulmonary embolism were confirmed by objective imaging. LR analysis, tree-based boosting and bagging were used to investigate the association of variables upon hospital presentation with VTE. Results: Among 4,120 patients (median age 61 [interquartile range 48-72] years-old, 55.5% men, 39.3% admitted to intensive care unit), VTE was confirmed in 6.7%. In multivariate LR analysis, obesity (OR 1.50, 95%CI 1.11-2.02); being an ex-smoker (OR 1.44, 95%CI 1.03-2.01); surgery ≤ 90 days (OR 2.20, 95%CI 1.14-4.23); axillary temperature (OR 1.41, 95%CI 1.22-1.63); D-dimer ≥ 4 times above the upper limit of reference value (OR 2.16, 95%CI 1.26-3.67), lactate (OR 1.10, 95%CI 1.02-1.19), C-reactive protein levels (CRP, OR 1.09, 95% CI 1.01-1.18); and neutrophil count (OR 1.04, 95%CI 1.005-1.075) were independent predictors of VTE. Temperature at hospital presentation, SF ratio, neutrophil count, D-dimer, CRP and lactate levels were also identified as predictors by ML methods. Conclusions: By using ML and LR analysis, we showed that D-dimer, axillary temperature, neutrophil count, CPR and lactate levels are risk factors for VTE in COVID-19 patients. ML approaches were able to identify additional predictors. We suggest that patients presenting those risk factors at hospital admission should be more closely monitored for VTE development.
Abstract 15522: Segmentation Improves Deep Learning Accuracy for Differentiating Non-Ischemic and Ischemic Cardiomyopathy Using Cardiac Mri Cine Imaging
Authors: Makiya Nakashima, Joshua Cockrum, Donna Salam, Samia Mazumder, Karthik Sreedhara, Samir R Kapadia, Lars G Svensson, Richard A Grimm, Christopher Nguyen, Wai Hong W Tang, David Chen, Deborah H Kwon
Journal: Circulation (2022)

Background: Deep learning (DL) models typically interpret images without prior knowledge of anatomic significance. However, pathophysiology is highly classified by human definitions according to underlying affected anatomy. Therefore, we examine the impact of introducing explicit knowledge of anatomy through cardiac contours on cardiac magnetic resonance images (CMR) to DL models. The DL models were then trained to differentiate between ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) using late gadolinium enhanced (LGE) CMR. Method: We evaluated 301 CMR studies; ICM (n=176) and NICM (n=125). Manual contouring of LGE images was performed using CVI42 (Circle, Ontario). We compared a radiomic and end-to-end DL approach to identify cardiomyopathy (CM) etiology from short axis LGE images. Patients are randomly assigned to training (70%) and testing (30%). Model performance was assessed with area under curve (AUC). Result: Table 1 shows the results of radiomic and deep learning approaches to differentiate NICM and ICM. Segmented/manually contoured images with removal of non-cardiac structures greatly improved classification accuracy across all deep learning models. The average improvement in AUC was 0.163 when using segmented images compared to the full images. Furthermore, the deep learning models outperformed the radiomics models. The best radiomic model and deep learning model achieved AUCs of 0.914 and 0.947, respectively. Both radiomic based models achieved AUCs above 0.874 while all 2D deep learning models with segmented images achieved AUCs above 0.875. The two 3D deep learning models which utilize 3D convolutions provided lower AUCs ranging between 0.743 and 0.900. Conclusion: Manual segmentation of LGE images improved the ability to train DL models with fairly small volumes of labeled data, resulting in higher classification accuracy. Table1 AUCs of various models.
Abstract 15663: Trasapical Mitral Valve and Left Ventricular Reshaping to Repair Functional Mitral Regurgitation in a Dilated Ventricle
Authors: Chase L King, Michael Silverman, Keawepono Wong, Yuta Kikuchi, Alejandra Lopez, Amanda Maddamma, Daisuke Onohara, Muralidhar Padala
Journal: Circulation (2022)

Background: The COAPT trial demonstrated that repair of functional mitral regurgitation (FMR) in heart failure (HF) improves prognosis, only when the LV end diastolic diameter is &lt;65mm. A significant need exists for a new therapy that can address both FMR and the LV in patients with LV EDD&gt;65mm. In this study, we report a novel beating heart transapical device that can address FMR by beating heart papillary muscle approximation (PMA), and reduces the LV size and sphericity as well. Preclinical efficacy of this novel device in a swine HF/FMR model is reported. Methods: The device was prototyped using biocompatible 3D printed parts (Fig A), and a delivery catheter was custom designed for beating heart deployment (Fig B). In 7 healthy pigs, and 4 pigs induced with chronic post-myocardial infarction HF, with moderate or greater FMR, the device was implanted via a transapical access. The device was adjusted in steps - (step 1) reduce the inter-PM distance to an extent that FMR is mild or less; and (step 2) reshape the LV to achieve a 30% reduction in LV EDV and 25% reduction in sphericity index (SI). Echocardiography was used to assess mitral valve function and LV geometry, and LV function was assessed with invasive hemodynamics. Pigs were survived thereafter. Results: With this new device, MR was consistently reduced from moderate levels to none/mild. Mitral valve coaptation length increased from 3.49 ± 0.42 to 6.45± 1.13 mm (p=.019) and tenting area decreased from 158.09± 33 to 116.4± 16.7mm 2 (p=.05). LV EDV was reduced from 142.8± 29.6 to 97.5± 19.6ml (p=.025), SI was decreased from 0.67± 0.04 to 0.49± 0.07 (p=.0497) and IPMD was reduced from 23.5± 5.7 to 12.76± 3.0mm (p=.032). The device did not adversely impact cardiac output (6.59± 1.3 to 4.83± 1.6 LPM, p=.067) or E/A wave ratio (1.40± 0.23 to 1.35±0.29, p=.60). Conclusion: This novel transapical beating heart MV and LV reshaping device, significantly reduced FMR and reshaped the LV in this swine model.
Abstract 16: Cardiac Mitochondrial Transcription Factor A Overexpression Protects Against Stunning and Improves Mortality in a Mouse Model of Cardiac Arrest
Authors: Cody A Rutledge, Sam Duvall, kevin redding, Cameron Dezfulian, Brett A Kaufman
Journal: Circulation (2022)

Background: Cardiac arrest (CA) affects over 600,000 Americans every year and is associated with overwhelming mortality. After CA, myocardial stunning is a common occurrence leading to reduced cardiac output, and nearly 25% of CA die from cardiogenic shock. This cardiac injury is driven by ischemia-reperfusion injury. Mitochondria make up 30% of the heart by volume and are highly prone to ischemia-reperfusion damage. This damage may impair mitochondrial DNA (mtDNA), which is necessary for maintaining mitochondrial function. Mitochondrial transcription factor A (TFAM) can bind and protect mtDNA from damage. In this study, we investigated the role of cardiac-specific TFAM overexpression on cardiac function after CA in a mouse model. Methods: Wild-type (WT) and transgenic mice featuring cardiac-specific TFAM overexpression (TFAM OE) were subjected to 8-min of asystole by direct injection of potassium chloride and were revived by cardiopulmonary resuscitation. Surviving mice were assessed by echocardiography and monitored for survival over 4 weeks frame. Hearts were collected and sent for bulk RNA sequencing as well as assessment of mtDNA copy number, mitochondrial morphology, and protein expression. Results: TFAM OE mice express 40% more TFAM than WT littermates. TFAM OE mice had protected cardiac EF (51.11±2.95%) one day after CA when compared to WT mice (38.49±3.76%) and improved survival over 4 weeks. Bulk-RNA sequencing implicated dramatic changes to ribosomal expression and protein synthesis in the arrest TFAM OE mice. Western blot analysis of 1-day post-arrest hearts demonstrated increased markers of mRNA translation, including increased phosphorylation of eukaryotic translation initiation factor 4E-binding protein (4E-BP1) and ribosomal protein S6, suggesting that TFAM OE mice support protein translation to aid in cardiac recovery after arrest. Conclusions: Cardiac TFAM overexpression protects cardiac function and survival after cardiac arrest. Early evidence suggests that this protection may be mediated by supporting protein translation, which may offer a novel pathway for improving outcomes after arrest.
Abstract 15506: Optical Mapping in Atrial Engineered Heart Tissues Reveals Proarrhythmic Potential of the Anti-AF Agent Vernakalant
Authors: Ilhan Gokhan, Afia Sarpong Frimpong, Marine Cacheux, Stuart G Campbell, Fadi G Akar
Journal: Circulation (2022)

Pharmacotherapy for atrial fibrillation (AF) is confounded by ventricular proarrhythmia. Vernakalant (VER) belongs to a class of atrial selective channel blockers developed in attempts to convert AF safely. Yet, robust analysis of the effects of VER in human based tissues has not been performed. We hypothesized that engineered heart tissues (EHT) composed of atrial (A) or ventricular (V) human iPSCs would provide a robust platform for quantitative analysis of chamber specific electrophysiological (EP) effects of VER. Methods: iPSCs were differentiated into cardiomyocytes using biphasic Wnt signaling, insulin, and lactate purification. Atrial-like myocytes were enriched by adding 0.75 μM retinoic acid on days 4-6 to promote atrial gene expression and specification. Myocytes were seeded onto cryosectioned, laser cut and decellularized myocardial tissues and cultured under isometric conditions. EHTs were stained with high dose, water soluble di-2-ANEPEQ to enhance signal-to-noise while avoiding toxicity. Results: Staining with 25 μM di-2-ANEPEQ provided high fidelity optical AP signals that allowed comprehensive characterization of the EP substrate. A-EHT exhibited significantly shorter AP durations than V-EHT reflecting greater repolarizing drive (APD80, 180 ms vs 367 ms; p &lt; 0.0001, n = 4-5). Consistent with its role as an atrial-selective blocker, VER increased APD80 only in A-EHTs (180 ms vs 258 ms, p = 0.0027, n = 5). This beneficial property for combatting AF was countered by marked slowing of A-EHT conduction and AP upstroke velocity (20.6 cm/s vs 11.7 cm/s, p = 0.027, n = 5). Conclusions: Optical mapping of chamber specific EHTs confirms atrial specific nature of VER as an atrial repolarization prolonging agent but raises unexpected concerns regarding potential proarrhythmic toxicity related to atrial conduction slowing.